Three-dimensional matrix-based models for dental tissue engineering

用于牙科组织工程的基于三维矩阵的模型

• 批准号: RGPIN-2020-05844
• 负责人: Kishen, Anil
• 金额: $ 3.1万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=750708
• 关键词: Three; dimensional; matrix; based; models

The availability of in vitro 3D (dimensional) cell-based models that mimics in vivo dento-alveolar tissues is a progressively significant challenge facing oral health research and dental industry. The rising total-delivered-cost as well as the poor predictive value of the current in vitro models and assays, place great emphasis on the development of more realistic 3D cell-based models and assays. Accurate and efficient in vitro models are of enormous value, since they permit early and knowledge-based decisions in drug testing. 3D matrix-based models with different cells, in a bioreactor system that simulate dentoalveolar system, holds great potential for tissue engineering, regenerative medicine and drug discovery. The main challenge in developing 3D dentoalveolar tissue constructs is the characterization of living, biologically relevant cells in the constructs and the application of environmental factors that mimics in vivo conditions. These models will confer the advantage of speed, accuracy and scale over existing 2D monoculture-based methods. These 3D model-based technologies are critically important for understanding disease process and drug discovery. My laboratory has recently emerged at the forefront of this nascent field due to our established work on nanomaterial characterization using cell culture-based models, experiments on stem cells from apical papillae, macrophages and macrophage-stem cell interactions. We have worked on the biomechanics of dento-osseous structures, which is key to simulate environmental factors in 3D dentoalveolar models. In addition, our recent efforts to adapt the rapidly emerging 3D printing technology to print molds, generated a novel way to position immune cells and stem cells in the 3D engineered dental tissue like constructs. Building on our established work and recent success, the short term aim of this research program is to develop and characterize in vitro 3D matrix-based tissue constructs in a bioreactor platform to simulate in vivo periodontium. Complementary rapid assays will be developed for determining cell morphology, migration, proliferation, differentiation and apoptosis. Using that understanding, we will focus on developing new anatomically-based designs to integrate immune/stem cells with extracellular matrix in the constructs of dentoalveolar apparatus. These models will aid in understanding the mechanisms of interaction between immune cells and stem cells in pro- and anti-inflammatory conditions, as well as in the presence of immune modulatory nanoparticles. Over the long term we will develop integrated in vitro 3D dentoalveolar tissue construct-bioreactor platform that lower the cost, increase throughput and automate rapid assays targeted towards specific applications in drug discovery or biological research. These systems by its cost effectiveness and enhanced capabilities will improve the productivity of pharmaceutical, biological and biomedical researchers

模拟体内牙槽组织的体外3D（三维）细胞模型的可用性是口腔健康研究和牙科行业面临的一个日益重要的挑战。不断上升的总交付成本以及目前体外模型和测定的预测价值差，非常重视开发更逼真的基于3D细胞的模型和测定。准确和有效的体外模型具有巨大的价值，因为它们允许药物测试中的早期和基于知识的决策。在模拟牙槽系统的生物反应器系统中，具有不同细胞的基于3D矩阵的模型在组织工程、再生医学和药物发现方面具有巨大的潜力。开发3D牙槽骨组织构建体的主要挑战是构建体中活的生物相关细胞的表征以及模拟体内条件的环境因素的应用。这些模型将在速度、准确性和规模上优于现有的基于2D单一文化的方法。这些基于3D模型的技术对于理解疾病过程和药物发现至关重要。我的实验室最近出现在这个新生领域的最前沿，这是由于我们使用基于细胞培养的模型对纳米材料进行表征的既定工作，对来自顶端乳头的干细胞，巨噬细胞和巨噬细胞-干细胞相互作用的实验。我们致力于牙-骨结构的生物力学研究，这是在三维牙槽骨模型中模拟环境因素的关键。此外，我们最近努力将快速新兴的3D打印技术应用于打印模具，产生了一种将免疫细胞和干细胞定位在3D工程化牙齿组织样结构中的新方法。基于我们的既定工作和最近的成功，本研究计划的短期目标是在生物反应器平台中开发和表征体外3D基质组织构建体，以模拟体内牙周组织。将开发用于确定细胞形态、迁移、增殖、分化和凋亡的补充快速测定法。利用这种理解，我们将专注于开发新的基于解剖学的设计，将免疫/干细胞与细胞外基质整合到牙槽骨结构中。这些模型将有助于理解免疫细胞和干细胞在促炎和抗炎条件下以及在免疫调节纳米颗粒存在下的相互作用机制。 从长远来看，我们将开发集成的体外3D牙槽组织构建-生物反应器平台，以降低成本，提高通量并自动化针对药物发现或生物研究中特定应用的快速测定。这些系统通过其成本效益和增强的能力将提高制药，生物和生物医学研究人员的生产力